Oncologic: Treatment of Hodgkin's and non-Hodgkin's lymphoma, Burkitt's lymphoma, chronic lymphocytic leukemia (CLL), chronic myelocytic leukemia (CML), acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), mycosis fungoides, multiple myeloma, neuroblastoma, retinoblastoma, rhabdomyosarcoma, Ewing's sarcoma; breast, testicular, endometrial, ovarian, and lung cancers, and in conditioning regimens for bone marrow transplantation
Nononcologic: Prophylaxis of rejection for kidney, heart, liver, and bone marrow transplants, severe rheumatoid disorders, nephrotic syndrome, Wegener's granulomatosis, idiopathic pulmonary hemosideroses, myasthenia gravis, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, autoimmune hemolytic anemia, idiopathic thrombocytic purpura (ITP), macroglobulinemia, and antibody-induced pure red cell aplasia
D Hypersensitivity to cyclophosphamide or any component of the formulation; pregnancy The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Dosage adjustment needed for renal or hepatic failure; use with caution in patients with bone marrow suppression.Cyclophosphamide preparation should be performed in a Class II laminar flow biologic safety cabinet. Personnel should be wearing surgical gloves and a closed front surgical gown with knit cuffs. Appropriate safety equipment is recommended for preparation, administration, and disposal of antineoplastics. If cyclophosphamide contacts the skin, wash and flush thoroughly with water.
>10%:
Dermatologic: Alopecia (40% to 60%) but hair will usually regrow although it may be a different color and/or texture. Hair loss usually begins 3-6 weeks after the start of therapy.
Endocrine & metabolic: Fertility: May cause sterility; interferes with oogenesis and spermatogenesis; may be irreversible in some patients; gonadal suppression (amenorrhea)
Gastrointestinal: Nausea and vomiting occur more frequently with larger doses, usually beginning 6-10 hours after administration; anorexia, diarrhea, mucositis, and stomatitis are also seen
Genitourinary: Severe, potentially fatal acute hemorrhagic cystitis or urinary fibrosis, believed to be a result of chemical irritation of the bladder by acrolein, a cyclophosphamide metabolite, occurs in 7% to 12% of patients and has been reported in up to 40% of patients in some series. Patients should be encouraged to drink plenty of fluids (3-4 L/day) during therapy, void frequently, and avoid taking the drug at night. With large I.V. doses, I.V. hydration is usually recommended. The use of mesna and/or continuous bladder irrigation is rarely needed for doses <2 g/m2.
Hematologic: Thrombocytopenia and anemia are less common than leukopenia
Onset: 7 days
Nadir: 10-14 days
Recovery: 21 days
1% to 10%:
Central nervous system: Headache
Dermatologic: Skin rash, facial flushing
Renal: SIADH may occur, usually with doses >50 mg/kg (or 1 g/m2); renal tubular necrosis, which usually resolves with discontinuation of the drug, is also reported
Respiratory: Nasal congestion occurs when I.V. doses are administered too rapidly (large doses via 30-60 minute infusion); patients experience runny eyes, rhinorrhea, sinus congestion, and sneezing during or immediately after the infusion. If needed, a decongestant or decongestant/antihistamine (eg, pseudoephedrine or pseudoephedrine/triprolidine) can be used to prevent or relieve these symptoms.
<1%: High-dose therapy may cause cardiac dysfunction manifested as CHF; cardiac necrosis or hemorrhagic myocarditis has occurred rarely, but may be fatal. Cyclophosphamide may also potentiate the cardiac toxicity of anthracyclines. Other adverse reactions include anaphylactic reactions, dizziness, darkening of skin/fingernails, hyperglycemia, hypokalemia, hyperuricemia, hepatotoxicity, jaundice, secondary malignancy, Stevens-Johnson syndrome, toxic epidermal necrolysis, hemorrhagic colitis, hemorrhagic ureteritis, renal tubular necrosis; interstitial pneumonitis and pulmonary fibrosis is occasionally seen with high doses
CYP2B6, 2D6, and 3A3/4 enzyme substrateDecreased effect: Digoxin: Cyclophosphamide may decrease digoxin serum levels
Increased toxicity:
Allopurinol may cause increase in bone marrow depression and may result in significant elevations of cyclophosphamide cytotoxic metabolites
Anesthetic agents: Cyclophosphamide reduces serum pseudocholinesterase concentrations and may prolong the neuromuscular blocking activity of succinylcholine; use with caution with halothane, nitrous oxide, and succinylcholine
Chloramphenicol results in prolonged cyclophosphamide half-life to increase toxicity
Cimetidine inhibits hepatic metabolism of drugs and may decrease or increase the activation of cyclophosphamide
Doxorubicin: Cyclophosphamide may enhance cardiac toxicity of anthracyclines
Phenobarbital and phenytoin induce hepatic enzymes and cause a more rapid production of cyclophosphamide metabolites with a concurrent decrease in the serum half-life of the parent compound
Tetrahydrocannabinol results in enhanced immunosuppression in animal studies
Thiazide diuretics: Leukopenia may be prolonged
Patients with compromised bone marrow function may require a 33% to 50% reduction in initial loading dose
Children:
SLE: I.V.: 500-750 mg/m2 every month; maximum dose: 1 g/m2
JRA/vasculitis: I.V.: 10 mg/kg every 2 weeks
Children and Adults:
Oral: 50-100 mg/m2/day as continuous therapy or 400-1000 mg/m2 in divided doses over 4-5 days as intermittent therapy
I.V.:
Single Doses: 400-1800 mg/m2 (30-50 mg/kg) per treatment course (1-5 days) which can be repeated at 2-4 week intervals
MAXIMUM SINGLE DOSE WITHOUT BMT is 7 g/m2(190 mg/kg) SINGLE AGENT THERAPY
Continuous daily doses: 60-120 mg/m2 (1-2.5 mg/kg) per day
Autologous BMT: IVPB: 50 mg/kg/dose x 4 days or 60 mg/kg/dose for 2 days; total dose is usually divided over 2-4 days
Nephrotic syndrome: Oral: 2-3 mg/kg/day every day for up to 12 weeks when corticosteroids are unsuccessful
Dosing adjustment in renal impairment: A large fraction of cyclophosphamide is eliminated by hepatic metabolism
Some authors recommend no dose adjustment unless severe renal insufficiency (Clcr<20 mL/minute)
Clcr >10 mL/minute: Administer 100% of normal dose
Clcr<10 mL/minute: Administer 75% of normal dose
Hemodialysis: Moderately dialyzable (20% to 50%); administer dose posthemodialysis or administer supplemental 50% dose
CAPD effects: Unknown
CAVH effects: Unknown
Dosing adjustment in hepatic impairment: Some authors recommend dosage reductions (of up to 30%); however, the pharmacokinetics of cyclophosphamide are not significantly altered in the presence of hepatic insufficiency. Cyclophosphamide undergoes hepatic transformation in the liver to its 4-hydroxycyclophosphamide, which breaks down to its active form, phosphoramide mustard.
Injection, powder for reconstitution: 100 mg, 200 mg, 500 mg, 1 g, 2 g
Tablet: 25 mg, 50 mg